Journal article
Astrocytes Play a Key Role in EAE Pathophysiology by Orchestrating in the CNS the Inflammatory Response of Resident and Peripheral Immune Cells and by Suppressing Remyelination
Glia, v 62(3), pp 452-467
01 Mar 2014
PMID: 24357067
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Astrocytes respond to insult with a process of cellular activation known as reactive astrogliosis. One of the key signals regulating this phenomenon is the transcription factor nuclear factor-kappa B (NF-B), which is responsible for modulating inflammation, cell survival, and cell death. In astrocytes, following trauma or disease, the expression of NF-B-dependent genes is highly activated. We previously demonstrated that inactivation of astroglial NF-B in vivo (GFAP-IB-dn mice) leads to improved functional outcome in experimental autoimmune encephalomyelitis (EAE), and this is accompanied by reduction of pro-inflammatory gene expression in the CNS. Here we extend our studies to show that recovery from EAE in GFAP-IB-dn mice is associated with reduction of peripheral immune cell infiltration into the CNS at the chronic phase of EAE. This is not dependent on a less permeable blood-brain barrier, but rather on a reduced immune cell mobilization from the periphery. Furthermore, once inside the CNS, the ability of T cells to produce pro-inflammatory cytokines is diminished during acute disease. In parallel, we found that the number of total and activated microglial cells is reduced, suggesting that functional improvement in GFAP-IB-dn mice is dependent upon reduction of the overall inflammatory response within the CNS sustained by both resident and infiltrating cells. This results in preservation of myelin compaction and enhanced remyelination, as shown by electron microscopy analysis of the spinal cord. Collectively our data indicate that astrocytes are key players in driving CNS inflammation and are directly implicated in the pathophysiology of EAE, since blocking their pro-inflammatory capability results in protection from the disease. GLIA 2014;62:452-467
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Details
- Title
- Astrocytes Play a Key Role in EAE Pathophysiology by Orchestrating in the CNS the Inflammatory Response of Resident and Peripheral Immune Cells and by Suppressing Remyelination
- Creators
- Roberta Brambilla - University of MiamiPaul D. Morton - University of MiamiJessica Jopek Ashbaugh - University of MiamiShaffiat Karmally - University of MiamiKate Lykke Lambertsen - University of Southern DenmarkJohn R. Bethea - University of Miami
- Publication Details
- Glia, v 62(3), pp 452-467
- Publisher
- Wiley
- Number of pages
- 16
- Grant note
- Danish MRC; Danish Medical Research Council Carlsbergfondet; Carlsberg Foundation Swiss IRP/IFP Foundation R01NS065479 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) Miami Project To Cure Paralysis R01 NS051709; R01 NS065479 / National Institute of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology; College of Arts and Sciences; Drexel University
- Web of Science ID
- WOS:000329822700009
- Scopus ID
- 2-s2.0-84892503390
- Other Identifier
- 991020099920104721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Neurosciences